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https://www.readbyqxmd.com/read/28540665/different-molecular-mechanisms-mediate-direct-or-glia-dependent-prion-protein-fragment-90-231-neurotoxic-effects-in-cerebellar-granule-neurons
#1
Stefano Thellung, Elena Gatta, Francesca Pellistri, Valentina Villa, Alessandro Corsaro, Mario Nizzari, Mauro Robello, Tullio Florio
Glia over-stimulation associates with amyloid deposition contributing to the progression of central nervous system neurodegenerative disorders. Here we analyze the molecular mechanisms mediating microglia-dependent neurotoxicity induced by prion protein (PrP)90-231, an amyloidogenic polypeptide corresponding to the protease-resistant portion of the pathological prion protein scrapie (PrP(Sc)). PrP90-231 neurotoxicity is enhanced by the presence of microglia within neuronal culture, and associated to a rapid neuronal [Ca(++)] i increase...
May 25, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28536975/a-new-hope-for-a-devastating-disease-hydrogen-sulfide-in-parkinson-s-disease
#2
REVIEW
Xu Cao, Lei Cao, Lei Ding, Jin-Song Bian
Hydrogen sulfide (H2S) has been regarded as the third gaseous transmitter alongside nitric oxide (NO) and carbon monoxide (CO). In mammalian brain, H2S is produced redundantly by four enzymatic pathways, implying its abundance in the organ. In physiological conditions, H2S has been found to induce the formation of long-term potential in neuronal cells by augmenting the activity of N-methyl-D-aspartate (NMDA) receptor. Likewise, it also actively takes part in the regulation of intracellular Ca(2+) and pH homeostasis in both neuronal cells and glia cells...
May 23, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28535798/using-kalirin-conditional-knockout-mice-to-distinguish-its-role-in-dopamine-receptor-mediated-behaviors
#3
Taylor P LaRese, Yan Yan, Betty A Eipper, Richard E Mains
BACKGROUND: Mice lacking Kalirin-7 (Kal7(KO)), a Rho GDP/GTP exchange factor, self-administer cocaine at a higher rate than wildtype mice, and show an exaggerated locomotor response to experimenter-administered cocaine. Kal7, which localizes to post-synaptic densities at glutamatergic synapses, interacts directly with the GluN2B subunit of the N-methyl-D-aspartate (NMDA; GluN) receptor. Consistent with these observations, Kal7 plays an essential role in NMDA receptor dependent long term potentiation and depression, and glutamatergic transmission plays a key role in the response to chronic cocaine...
May 23, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28534738/optocontrol-of-glutamate-receptor-activity-by-single-side-chain-photoisomerization
#4
Viktoria Klippenstein, Christian Hoppmann, Shixin Ye, Lei Wang, Pierre Paoletti
Engineering light-sensitivity into proteins has wide ranging applications in molecular studies and neuroscience. Commonly used tethered photoswitchable ligands, however, require solvent-accessible protein labeling, face structural constrains, and are bulky. Here, we designed a set of optocontrollable NMDA receptors by directly incorporating single photoswitchable amino acids (PSAAs) providing genetic encodability, reversibility, and site tolerance. We identified several positions within the multi-domain receptor endowing robust photomodulation...
May 23, 2017: ELife
https://www.readbyqxmd.com/read/28534043/familiarity-detection-is-an-intrinsic-property-of-cortical-microcircuits-with-bidirectional-synaptic-plasticity
#5
Xiaoyu Zhang, Han Ju, Trevor B Penney, Antonius M J VanDongen
Humans instantly recognize a previously seen face as "familiar." To deepen our understanding of familiarity-novelty detection, we simulated biologically plausible neural network models of generic cortical microcircuits consisting of spiking neurons with random recurrent synaptic connections. NMDA receptor (NMDAR)-dependent synaptic plasticity was implemented to allow for unsupervised learning and bidirectional modifications. Network spiking activity evoked by sensory inputs consisting of face images altered synaptic efficacy, which resulted in the network responding more strongly to a previously seen face than a novel face...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28533163/grin2b-gain-of-function-mutations-are-sensitive-to-radiprodil-a-negative-allosteric-modulator-of-glun2b-containing-nmda-receptors
#6
Brice Mullier, Christian Wolff, Zara Amanda Sands, Philippe Ghisdal, Pierandrea Muglia, Rafal Marian Kaminski, Véronique Marie André
De novo gain of function mutations in GRIN2B encoding the GluN2B subunit of the N-methyl-D-aspartate (NMDA) receptor have been linked with epileptic encephalopathies, including infantile spasms. We investigated the effects of radiprodil, a selective GluN2B negative allosteric modulator and other non-selective NMDA receptor inhibitors on glutamate currents mediated by NMDA receptors containing mutated GluN2B subunits. The experiments were performed in Xenopus oocytes co-injected with the following human mRNAs: GRIN1/GRIN2B, GRIN1/GRIN2B-R540H, GRIN1/GRIN2B-N615I and GRIN1/GRIN2B-V618G...
May 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28533113/a-novel-serine-racemase-inhibitor-suppresses-neuronal-over-activation-in-vivo
#7
Hisashi Mori, Ryogo Wada, Satoyuki Takahara, Yoshikazu Horino, Hironori Izumi, Tetsuya Ishimoto, Tomoyuki Yoshida, Mineyuki Mizuguchi, Takayuki Obita, Hiroaki Gouda, Shuichi Hirono, Naoki Toyooka
Serine racemase (SRR) is an enzyme that produces d-serine from l-serine. d-Serine acts as an endogenous coagonist of NMDA-type glutamate receptors (NMDARs), which regulate many physiological functions. Over-activation of NMDARs induces excitotoxicity, which is observed in many neurodegenerative disorders and epilepsy states. In our previous works on the generation of SRR gene knockout (Srr-KO) mice and its protective effects against NMDA- and Aβ peptide-induced neurodegeneration, we hypothesized that the regulation of NMDARs' over-activation by inhibition of SRR activity is one such therapeutic strategy to combat these disease states...
May 11, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28526038/phosphorylation-of-tau-at-y18-but-not-tau-fyn-binding-is-required-for-tau-to-modulate-nmda-receptor-dependent-excitotoxicity-in-primary-neuronal-culture
#8
Takashi Miyamoto, Liana Stein, Reuben Thomas, Biljana Djukic, Praveen Taneja, Joseph Knox, Keith Vossel, Lennart Mucke
BACKGROUND: Hyperexcitability of neuronal networks can lead to excessive release of the excitatory neurotransmitter glutamate, which in turn can cause neuronal damage by overactivating NMDA-type glutamate receptors and related signaling pathways. This process (excitotoxicity) has been implicated in the pathogenesis of many neurological conditions, ranging from childhood epilepsies to stroke and neurodegenerative disorders such as Alzheimer's disease (AD). Reducing neuronal levels of the microtubule-associated protein tau counteracts network hyperexcitability of diverse causes, but whether this strategy can also diminish downstream excitotoxicity is less clear...
May 19, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28524267/synaptic-activity-suppresses-expression-of-neurogenic-differentiation-factor-2-in-an-nmda-receptor-dependent-manner
#9
Fading Chen, Benjamin J Hall
Neurogenic differentiation factor 2 (NeuroD2) is a highly expressed transcription factor in the developing central nervous system. In newborn neurons, NeuroD2-mediated gene expression promotes differentiation, maturation, and survival. In addition to these early, cell-intrinsic developmental processes, NeuroD2 in post-mitotic neurons also regulates synapse growth and ion channel expression to control excitability. While NeuroD2 transactivation can be induced in an activity-dependent manner, little is known about how expression of NeuroD2 itself is regulated...
May 19, 2017: Synapse
https://www.readbyqxmd.com/read/28512009/combining-d-cycloserine-with-appetitive-extinction-learning-modulates-amygdala-activity-during-recall
#10
Claudia Ebrahimi, Stefan P Koch, Eva Friedel, Ilsoray Crespo, Thomas Fydrich, Andreas Ströhle, Andreas Heinz, Florian Schlagenhauf
Appetitive Pavlovian conditioning plays a crucial role in the pathogenesis of drug addiction and conditioned reward cues can trigger craving and relapse even after long phases of abstinence. Promising preclinical work showed that the NMDA-receptor partial agonist D-cycloserine (DCS) facilitates Pavlovian extinction learning of fear and drug cues. Furthermore, DCS-augmented exposure therapy seems to be beneficial in various anxiety disorders, while the supposed working mechanism of DCS during human appetitive or aversive extinction learning is still not confirmed...
May 13, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28511693/antagonistic-action-on-nmda-glun2b-mediated-currents-of-two-peptides-that-were-conantokin-g-structure-based-designed
#11
Edwin A Reyes-Guzman, Nohora Vega-Castro, Edgar A Reyes-Montaño, Esperanza Recio-Pinto
BACKGROUND: The GluN2B subunit of the N-methyl-D-aspartate receptor (NMDAr) modulates many physiological processes including learning, memory, and pain. Excessive increase in NMDAr/GluN2B activity has been associated with various disorders such neuropathic pain and neuronal death following hypoxia. Thus there is an interest in identifying NMDAr antagonists that interact specifically with the GluN2B subunit. Recently based on structural analysis between the GluN2B subunit and conantokin-G, a toxin that interacts selectively with the GluN2B subunit, we designed various peptides that are predicted to act as NMDAr antagonists by interacting with the GluN2B subunit...
May 16, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28511005/characterization-of-l-theanine-excitatory-actions-on-hippocampal-neurons-towards-the-generation-of-novel-n-methyl-d-aspartate-receptor-modulators-based-on-its-backbone
#12
Fatiha Sebih, Matthieu Rousset, Salima Bellahouel, Marc Rolland, Marie Celeste de Jesus Ferreira, Janique Guiramand, Catherine Cohen-Solal, Gérard Barbanel, Thierry Cens, Mohammed Abouazza, Adrien Tassou, Maud Gratuze, Céline Meunier, Pierre Charnet, Michel Vignes, Valérie Rolland
L-Theanine (or L-γ-N-ethyl-glutamine) is the major amino acid found in Camellia sinensis. It has received much attention because of its pleiotropic physiological and pharmacological activities leading to health benefits in humans, especially. We describe here a new, easy, efficient and environmentally-friendly chemical synthesis of L-Theanine and L-γ-N-propyl-Gln and their corresponding D isomers. L-Theanine, and its derivatives obtained so far, exhibited partial co-agonistic action at N-methyl-D-aspartate (NMDA) receptors, with no detectable agonist effect at other glutamate receptors, on cultured hippocampal neurons...
May 16, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28508887/an-evolutionary-switch-in-nd2-enables-src-kinase-regulation-of-nmda-receptors
#13
David P Scanlon, Alaji Bah, Mickaël Krzeminski, Wenbo Zhang, Heather L Leduc-Pessah, Yi Na Dong, Julie D Forman-Kay, Michael W Salter
The non-receptor tyrosine kinase Src is a key signalling hub for upregulating the function of N-methyl D-aspartate receptors (NMDARs). Src is anchored within the NMDAR complex via NADH dehydrogenase subunit 2 (ND2), a mitochondrially encoded adaptor protein. The interacting regions between Src and ND2 have been broadly identified, but the interaction between ND2 and the NMDAR has remained elusive. Here we generate a homology model of ND2 and dock it onto the NMDAR via the transmembrane domain of GluN1. This interaction is enabled by the evolutionary loss of three helices in bilaterian ND2 proteins compared to their ancestral homologues...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28507513/appetitive-olfactory-learning-and-long-term-associative-memory-in-caenorhabditis-elegans
#14
Saori Nishijima, Ichiro N Maruyama
Because of the relative simplicity of its nervous system, Caenorhabditis elegans is a useful model organism to study learning and memory at cellular and molecular levels. For appetitive conditioning in C. elegans, food has exclusively been used as an unconditioned stimulus (US). It may be difficult to analyze neuronal circuits for associative memory since food is a multimodal combination of olfactory, gustatory, and mechanical stimuli. Here, we report classical appetitive conditioning and associative memory in C...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28506554/selective-dopamine-receptor-4-activation-mediates-the-hippocampal-neuronal-calcium-response-via-ip3-and-ryanodine-receptors
#15
Ya-Li Wang, Jian-Gang Wang, Fang-Li Guo, Xia-Huan Gao, Dan-Dan Zhao, Lin Zhang, Jian-Zhi Wang, Cheng-Biao Lu
Intracellular calcium is a key factor in most cellular processes, including cell growth, differentiation, proliferation and neurotransmitter release. Dopamine (DA) mediates synaptic transmission by regulating the intracellular calcium content. It is not clear, however, which specific subunit of the DA receptor contributes to DA modulation of intracellular calcium content changes. Through the traditional technique of Fura-2 calcium imaging, this study demonstrated that the DA can induce transient calcium in cultured hippocampal neurons and that this response can be mimicked by a selective dopamine receptor 4 (DR4) agonist PD168077 (PD)...
May 12, 2017: Brain Research
https://www.readbyqxmd.com/read/28500623/simultaneous-inhibition-of-nmda-and-mglu1-5-receptors-by-levo-corydalmine-in-rat-spinal-cord-attenuates-bone-cancer-pain
#16
Wen-Ling Dai, Bing Yan, Nan Jiang, Juan-Juan Wu, Xiu-Feng Liu, Ji-Hua Liu, Bo-Yang Yu
Bone cancer pain is a challenge for its not completely clarified mechanism and broad clinical morbidity. Therefore, novel and more effective drugs are urgent needed for improvement of patients' quality of life. Glutamate receptors have been associated with the development of the central sensitization of chronic pain. Inhibition of N-methyl-D-aspartate (NMDA) and metabotropic glutamate (mGlu) receptors can effectively attenuate bone cancer pain respectively. Herein, our results indicated that levo-Corydalmine (l-CDL), a compound from Corydalis yanhusuo W...
May 13, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28497343/bdnf-contributes-to-spinal-long-term-potentiation-and-mechanical-hypersensitivity-via-fyn-mediated-phosphorylation-of-nmda-receptor-glun2b-subunit-at-tyrosine-1472-in-rats-following-spinal-nerve-ligation
#17
Song Li, Jie Cai, Zhi-Bo Feng, Zi-Run Jin, Bo-Heng Liu, Hong-Yan Zhao, Hong-Bo Jing, Tian-Jiao Wei, Guan-Nan Yang, Ling-Yu Liu, Yan-Jun Cui, Guo-Gang Xing
Previously we have demonstrated that brain-derived neurotrophic factor (BDNF) contributes to spinal long-term potentiation (LTP) and pain hypersensitivity through activation of GluN2B-containing N-methyl-D-aspartate (GluN2B-NMDA) receptors in rats following spinal nerve ligation (SNL). However, the molecular mechanisms by which BDNF impacts upon GluN2B-NMDA receptors and spinal LTP still remain unclear. In this study, we first documented that Fyn kinase-mediated phosphorylation of GluN2B subunit at tyrosine 1472 (pGluN2B(Y1472)) was involved in BDNF-induced spinal LTP and pain hypersensitivity in intact rats...
May 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28495529/mek-erk-and-calcineurin-nfat-mediated-mechanism-of-cerebral-hyperemia-and-brain-injury-following-nmda-receptor-activation
#18
Yuki Kurauchi, Rintaro Kinoshita, Asami Mori, Kenji Sakamoto, Tsutomu Nakahara, Kunio Ishii
N-methyl-d-aspartate (NMDA) receptor activation increases regional cerebral blood flow (rCBF) and induces neuronal injury, but similarities between these processes are poorly understood. In this study, by measuring rCBF in vivo, we identified a clear correlation between cerebral hyperemia and brain injury. NMDA receptor activation induced brain injury as a result of rCBF increase, which was attenuated by an inhibitor of mitogen-activated protein kinase or calcineurin. Moreover, NMDA induced phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear translocation of nuclear factor of activated T-cell (NFAT) in neurons...
May 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28495142/n-methyl-d-aspartate-receptor-mediated-calcium-overload-and-endoplasmic-reticulum-stress-are-involved-in-interleukin-1beta-induced-neuronal-apoptosis-in-rat-hippocampus
#19
Yilong Dong, Allan V Kalueff, Cai Song
Increased levels of interleukin (IL)-1β and its gene expression are implicated in the etiology of Alzheimer's disease (AD). IL-1β activates microglia and stimulates glutamatergic N-methyl-d-aspartate receptor NMDA receptor expression, thereby disturbing intracellular Ca(2+) homeostasis. Ca(2+) disequilibrium, in turn, may trigger endoplasmic reticulum (ER) stress, contributing to overall excitotoxicity and neuronal death that evoke AD. However, it is unclear whether IL-1β-induced neuronal apoptosis is mediated by the glutamatergic system, ER stress and/or Ca(2+) dysfunction...
June 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28486923/kynurenic-acid-and-neuroprotective-activity-of-the-ketogenic-diet-in-the-eye
#20
Tomasz Żarnowski, Maria Tulidowicz-Bielak, Iwona Żarnowska, Krystyna Mitosek-Szewczyk, Artur Wnorowski, Krzysztof Jóźwiak, Maciej Gasior, Waldemar A Turski
There is growing evidence of the involvement of the kynurenine metabolic pathway and the enhancement of kynurenic acid (KYNA) production in the neuroprotective effects of the ketogenic diet (KD). KD and ketone bodies (KBs) that are elevated during exposure to the KD each have a neuroprotective effect on retinal ganglion cells in a rat model of N-methyl-D-aspartate (NMDA)-induced neuronal damage. Chronic exposure to KD also increases KYNA concentrations in discrete rat brain structures. A non-selective glutamate receptor agonist, glutamate, also decreases the production of KYNA in bovine retinal slices; this effect is attenuated by acetoacetate and β-hydroxybutyrate, two of three KBs overproduced during KD...
May 9, 2017: Current Medicinal Chemistry
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